Factors influencing lopinavir and atazanavir plasma concentration

Stöhr, Wolfgang, Back, David, Dunn, David, Sabin, Caroline, Winston, Alan, Gilson, Richard, Pillay, Deenan, Hill, Teresa, Ainsworth, Jonathan, Gazzard, Brian, Leen, Clifford, Bansi, Loveleen, Fisher, Martin, Orkin, Chloe, Anderson, Jane, Johnson, Margaret, Easterbrook, Philippa, Gibbons, Sara and Khoo, Saye (2010) Factors influencing lopinavir and atazanavir plasma concentration. The Journal of antimicrobial chemotherapy, 65 (1). pp. 129-137. ISSN 1460-2091

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Abstract

BACKGROUND

The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration.

METHODS

Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake.

RESULTS

Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54).

CONCLUSIONS

This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RC Internal medicine > RC0109 Infectious and parasitic diseases
Depositing User: Ellen Thomas
Date Deposited: 05 Aug 2013 13:06
Last Modified: 05 Aug 2013 13:06
URI: http://sro.sussex.ac.uk/id/eprint/45621
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